Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To analyze the clinical outcomes of initial radioactive iodine 131I therapy (RIT) for patients with familial differentiated thyroid cancer (FDTC) and sporadic differentiated thyroid cancer (SDTC), along with their influencing factors. Methods:The clinical data of 120 FDTC and 480 SDTC patients who received RIT at the Department of Nuclear Medicine, Tianjin Medical University General Hospital from January 2016 to January 2022 were retrospectively analyzed. These patients, categorized into the FDTC and SDTC groups, were further divided into three subgroups based on their response to initial RIT: no evidence of disease (NED), biochemical persistence of disease (BPD), or structural/functional persistence of disease (S/FPD). For the NED subgroup, the disease-free survival (DFS) was analyzed. For the BPD and S/FPD subgroups, the progression-free survival (PFS) was investigated. Furthermore, risk factors for failure to reach the NED status were identified.Results:After initial RIT, 56 (46.7%), 50 (41.7%), 14 (11.6%) patients in the FDTC group reached the NED, BPD, and S/FPD statuses, respectively, while 284 (59.1%), 160 (33.3%), 36 (7.5%) and SDTC patients in the SDTC group were in the NED, BPD, and S/FPD statuses, respectively ( χ2 = 10.10, P = 0.013). The last follow-up revealed that 71 (59.1%), 36 (30.1%), 13 (10.8%) patients in the FDTC group were in the NED, BPD and S/FPD statuses, respectively, while 337 (70.2%), 114 (23.7%), 29 (6.1%) patients in the SDTC group reached the NED, BPD and S/FPD statuses, respectively ( χ2 = 8.99, P = 0.026). The F-NED and S-NED subgroups exhibited 5-year DFS rates of 92.4% and 97.4%, respectively, the F-BPD and S-BPD subgroups displayed 5-year PFS rates of 88.3% and 90.8%, respectively, while the F-S/FPD and S-S/FPD subgroups yielded in 5-year PFS rates of 78.2% and 79.6%, respectively. Univariate binary logistic regression analysis indicated that the maximum diameter of tumors, T stage, M stage, recurrence risk stratification, and postoperative stimulated thyroglobulin (p-sTg) were correlated with the achievement of the NED status ( χ2=6.37-13.10, P < 0.05). Multivariable binary logistic regression analysis showed that T stage and p-sTg were independent risk factors in the achievement of the NED status ( χ2=0.11-11.33, P < 0.05). Conclusions:The response to initial RIT assists in guiding the development of subsequent treatment and follow-up strategies for DTC patients. Given that the SDTC patients exhibited better outcomes than the FDTC patients, more alertness should be paid to the RIT for FDTC patients. For patients with higher p-sTg and T stage, the initial RIT dose and follow-up interval should be increased and reduced respectively as appropriate.

Objective:To explore the effects of hospital-to-community model-based case management on outcomes and life quality of patients with atrial fibrillation.Methods:By convience sampling method, a total of 90 cases of atrial fibrillation patients admitted to Changzhou Second People′s Hospital from January 2019 to May 2020 were randomly divided into control group and experimental group, with 45 cases in each group. The patients in the control group received routine nursing care, the experimental group implemented hospital-to-community model-based case management. The beliefs about medicine, medication compliance, quality of life and readmissions of cardiovascular events were compared between 2 groups before and 6 months after intervention.Results:Finally, 41 cases were included in the experimental group and 38 cases in the control group. Before intervention, there were no significant differences in various indexes between the two groups ( P>0.05). After 6 months of intervention, the scores of specific-necessity in Beliefs about Medicines Questionnaire-Specific (BMQ-Specific) and Morisky Medication Adherence Scale-8 (MMAS-8) were (16.98 ± 4.22) and (7.15 ± 0.69) points in the experimental group, higher than in the control group (14.95 ± 4.33) and (6.32 ± 1.07) points; the scores of specific-concerns in BMQ-Specific were (6.83 ± 1.91)points in the experimental group, lower than in the control group (8.42 ± 2.73) points. The differences were statistically significant ( t = 2.11, 4.07, 2.98, all P<0.05); the scores of physical function, role-physical, pain, general health, mental health dimensions and total scores in SF-36 were (80.37 ± 3.46), (46.63 ± 14.54), (90.37 ± 5.78), (70.07 ± 9.98), (84.20 ± 8.73) and (584.88 ± 25.71) points in the experimental group, higher than in the control group (70.13 ± 11.20), (37.34 ± 10.25), (83.37 ± 6.89), (59.55 ± 7.98), (77.58 ± 9.09) and (533.87 ± 31.62) points, the differences were statistically significant ( t values were 3.30-7.89, all P<0.05). At 6 months after discharge, the re-admission of cardiovascular events were 5 cases (12.2%) in the experimental group and 12 cases (31.6%) in the control group, the difference was statistically significant ( χ2=4.74, P<0.05). Conclusions:Hospital-to-community model-based case management can effectively promote beliefs about medicine and medication compliance, improve quality of life and decrease re-admission of cardiovascular events of patients with atrial fibrillation.

Objective:To explore the optimum time of ambulation of atrial fibrillation patients after radiofrequency ablation, to provide basis for patients' early postoperative rehabilitation.Methods:By convenient sampling method, a total of 120 patients with atrial fibrillation after radiofrequency ablation were collected at Yanghu Branch and City Branch of Changzhou Second People's Hospital from January 2020 to May 2021. They were divided into the early group, middle group and late group according to the random number table method, each group were 40 cases. All patients received routine postoperative intervention, the time of ambulation were 4, 6 and 12 h after operation in the early group, middle group and late group, respectively. The complication rate within 24 h after operation was compared among the three groups, and the comfort level of the three groups at 24, 48 and 72 h after operation was evaluated with Comfort Status Scale (GCQ).Results:Finally, 111 patients were included, including 37 in the early group, 38 in the middle group and 36 in the late group. There was no significant difference in the incidence of bleeding or hematoma, urinary retention, lumbago within 24 h after operation among the three groups ( P>0.05). The incidence of postural hypotension within 24 h after operation in the early group was 2.7% (1/37), which was lower than 21.1% (7/38) and 25.0% (9/36) in the middle and late groups, with a statistically significant difference ( χ2=4.86, 7.67, both P<0.05). At 48 and 72 h after operation, the scores of physiological dimension, psychological dimension and the total score of GCQ in the early group were (20.68 ± 3.07), (22.54 ± 3.35), (81.68 ± 6.11) and (22.54 ± 3.73), (24.38 ± 2.49), (84.92 ± 6.37), higher than those in the middle group (19.16 ± 2.19), (21.32 ± 2.27), (78.24 ± 5.58), (20.93 ± 2.85), (22.32 ± 2.04), (81.66 ± 6.56), and those in the late group (18.44 ± 1.50) (21.31 ± 1.99), (78.06 ± 4.32), (20.89 ± 2.25), (21.58 ± 1.86), (80.28 ± 6.44), the differences were statistically significant ( t values were 2.19-4.15, all P<0.05). Conclusions:Ambulation at 4 h after operation does not increase peripheral vascular complications, but can reduce the incidence of postural hypotension and improve the comfort of patients with atrial fibrillation after radiofrequency ablation.

Objective:To analyze the short-term effect of targeted drugs on quality of life in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:From February 2020 to April 2022, 19 RAIR-DTC patients (10 males, 9 females; age (54.5±14.5) years) who received targeted drugs therapy (sorafenib, lenvatinib or anlotinib) in Tianjin Medical University General Hospital were prospectively enrolled. The thyroglobulin (Tg) levels prior and 1, 3, 6 months post the targeted treatment, and the adverse events were measured and recorded. Response evaluation criteria in solid tumors (RECIST) 1.1 version was used to evaluate the treatment response. The quality of life based on five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was monitored prior and 3 months post the targeted treatment, and the prevalence rates of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were analyzed, and the scores of health assessment were assessed. Paired t test, Kruskal-Wallis rank sum test and χ2 test were used to analyze data. Results:The prevalence rates of mobility (8/19), self-care (6/19), usual activities (10/19), pain/discomfort (10/19), and anxiety/depression (12/19) in 3 months post treatment were higher than those prior treatment (1/19, 1/19, 1/19, 2/19, 2/19; χ2 values: 4.38-11.31, all P<0.05). The score of health assessment prior treatment was (84.37±6.25), which was higher than that at 3 months post treatment (71.63±9.14; t=5.02, P=0.001). After targeted treatment, 10 patients were with skin toxicity, 8 patients were with hypertension, 8 patients were with weight loss, 7 patients were with diarrhea, 6 patients were with fatigue, 5 patients were with hepatic dysfunction, 2 patients were with proteinuria, 2 patients were with muscle pain and 1 patient was with oral ulcer. Of 19 patients, 17 insisted on continuing treatment, and the other two stopped treatment. The Tg levels at 1, 3 and 6 months post treatment were 56.26(44.60, 210.50), 53.36(41.25, 203.07) and 54.35(34.71, 223.52) mg/L, respectively, which were lower than the level prior treatment with no significant difference (110.16(49.63, 294.50) mg/L; H=2.42, P=0.490). After 3 months of targeted treatment, the progression-free survival (PFS) rate was 16/17, including 7 patients with partial response (PR), 9 patients with stable disease (SD), and 1 patient with progression of disease (PD). After 6 months of targeted treatment, the PFS rate was 10/17, including 5 patients with PR, 5 patients with SD, and 7 patients with PD. Conclusion:After 3-6 months of targeted treatment, the tumor markers of most patients are decreased with metastases improved, but the adverse events of targeted drugs have a great impact on quality of life in patients with RAIR-DTC.

Objective:To analyze the incidence of eating problems and risk factors in children aged 1-6 years, and provide evidence for formulating relevant prevention and control strategies.Methods:From June to December 2019, two community health service centers and two kindergartens were randomly selected in Shunyi district of Beijing by using stratified random cluster sampling method. Self-designed questionnaires were used to collect data on individual information, family information, and the incidence of eating problems and related factors. Multivariable logistic regression analysis was conducted to identify related factors.Results:A total of 2 391 valid questionnaires were returned, the analysis result indicated that 1 432 children had at least one eating behavior problem, the incidence rate was 59.9 %. The most common eating problem was inattention while eating (48.8 %), followed by irregular eating position (14.0 %), picky eaters (13.0 %), excessive eating time (11.2 %), excessive snacks intake (9.0 %), and soup with rice (4.6 %). The mother’s education level, family income level, main caregivers and family members’ attitudes toward child’s eating were related factors for eating behavior problems in children. Mothers with high education level ( OR=0.528, 95 %CI: 0.431-0.647) and family with high income level ( OR=0.656, 95 %CI: 0.473- 0.909) were the protective factors for child’s poor eating behaviors. Grandparent caring ( OR=1.366, 95 %CI: 1.151-1.622), coaxing or forcing child to eat ( OR=1.581, 95 %CI: 1.284-1.947) were the risk factors for child’s poor eating behavior. Conclusion:The incidence of eating problems was high in children aged 1-6 years. It is necessary to strengthen the intervention in families with low-income and low-education levels and children raised by grandparents to reduce the incidence of poor eating behaviors in children.

Objective To explore the relationship and influencing factors between pre‐diabetes mellitus (pre‐DM) and hypertension, providing evidence for formulating strategies for cardiovascular disease prevention and control. Methods We conducted this study from June 2013 to September 2014. Using stratified multistage random sampling, participants were administered a questionnaire survey, their height, weight, waist circumference, hip circumference, other physical attributes, blood pressure and blood lipids were measured. They also underwent the 75‐g glucose tolerance test and other laboratory examinations. A logistic regression model was used to analyze the relationship between pre‐DM and hypertension and its influencing factors. Results A total of 4 002 participants completed the survey. Participants'mean age was 50.3 ± 11.8 years. Of the total participants, 1 962 (49.0%) were males, while 2 039 (51.0%) were females; 1 participant had missing gender data. Further, 2 188 participants had normal glucose metabolism, 1 066 had pre‐DM, and 748 had diabetes. The prevalence of hypertension in participants with normal glucose metabolism, impaired fasting glucose, impaired glucose tolerance, both impaired fasting glucose and impaired glucose tolerance, and DM was 28.3%, 46.5%, 46.3%, 62.0%, and 61.2%, respectively. The prevalence of hypertension varied among people with different glucose metabolism (χ2=306.672, P<0.001). The prevalence of hypertension in the pre‐DM population increased with the aggravation of abnormal glucose metabolism compared to the normal glucose metabolism population, with a linear trend (χ2=299.009, P<0.001). Among those with abnormal glucose metabolism, there were differences in age, cholesterol, triglycerides, low‐density lipoproteins, body mass index, and waist circumference compared to those without hypertension (P<0.05). The risk of hypertension in the pre‐diabetic population was 1.5 times higher than that in the normal glucose metabolism population (OR=2.510, 95% CI: 2.156-2.922, P<0.001). There was no difference in the correlation intensity between pre‐DM and hypertension when gender was taken into account. Age and lipid abnormalities slightly decreased the correlation intensity between abnormal glucose metabolism and hypertension. Considering body mass index and centripetal obesity, the correlation intensity between abnormal glucose metabolism and hypertension could be reduced by controlling these factors. Conclusion The prevalence of hypertension is high in people with pre‐DM. There is a correlation between pre‐DM and hypertension, even when considering factors such as age, dyslipidemia, body mass index, and centripetal obesity. Therefore, it is necessary to strengthen the management of blood pressure in the pre‐diabetic population; improve early intervention for risk factors such as dyslipidemia, body mass index, and centripetal obesity; and reduce the occurrence of hypertension.

Vascular endothelial growth factor,hypoxia inducible factor,interleukin,angiopoietin-like protein,integrin and epithelial mesenchymal transition can provide nutritional support and favorable environment for the growth,invasion and metastasis of cancer cells.Researches about mechanisms of the angiogenesis in esophageal squamous cell carcinoma may provide more ideas and potential targets for the anti-angiogenesis targeted therapy.

Objective To investigate whether homocysteine (Hcy) level in the acute phase of stroke influences the recurrence of stroke and mortality of the patients. Methods A total of 3799 patients with first-onset ischemic stroke, admitted to our hospital from September 2005 to March 2011, were recruited;their demographic information, comorbidities, and clinical data were collected;Hcy level was measured within 24 h of primary admission. According to the Hcy level, patients were divided into normal Hcy group (Hcy<15 μmol/L, n=2267), and hyperhomocysteinemia (HHcy) group (Hcy≥15μmol/L, n=1532). Patients were followed up for three years, univariate analysis and Cox proportional hazards regression analysis were used to analyze the relations of Hcy level with recurrence and mortality. Results During the three years of follow-up, 702 patients suffered recurrent stroke, and 303 died. The HHcy group had significantly higher recurrence stroke rate (21.8%vs. 16.2%) and mortality (11.2%vs. 5.8%) than the normal Hcy group (P<0.05). After being adjusted for age, gender, diabetes, hyperlipidemia, drinking, smoking, hyperuricemia, low density lipoprotein level, apolipoprotein B/apolipoprotein AI ratio and fasting blood glucose level, patients in the HHcy group had significantly increased risk of recurrent stroke (hazard ratio[HR]=1.101, 95%CI: 1.037-1.257, P=0.002) and mortality (HR=1.701, 95%CI: 1.040-2.283, P=0.000) than patients in the normal Hcy group. Further subgroup analysis showed that this correlation was only significant in the large artery atherosclerosis stroke subtype:the recurrent stroke risk (adjusted HR=1.071, 95%CI:1.037-1.106, P=0.003) and mortality risk (HR=1.86, 95%CI:1.12-2.97, P=0.001) in the HHcy group were significantly higher than those in normal Hcy group;however, in small-vessel occlusion subtype, the risk of recurrence stroke (HR=0.731, 95%CI:0.043-1.205, P=0.058) and mortality risk(HR=0.77, 95%CI:0.29-2.34, P=0.061) in the HHcy group were not significant as compared with those in the normal Hcy group. Conclusions Hcy level is a risk factor for stroke recurrence and mortality in patients with acute ischemic stroke.